AU2018349093A1 - T cell-antigen coupler with Y182T mutation and methods and uses thereof - Google Patents
T cell-antigen coupler with Y182T mutation and methods and uses thereof Download PDFInfo
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- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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- C—CHEMISTRY; METALLURGY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
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- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- C—CHEMISTRY; METALLURGY
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- C07K2318/00—Antibody mimetics or scaffolds
- C07K2318/20—Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics
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- C—CHEMISTRY; METALLURGY
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- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
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- C—CHEMISTRY; METALLURGY
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- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16041—Use of virus, viral particle or viral elements as a vector
- C12N2740/16043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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| US201762571354P | 2017-10-12 | 2017-10-12 | |
| US62/571,354 | 2017-10-12 | ||
| PCT/CA2018/051290 WO2019071358A1 (en) | 2017-10-12 | 2018-10-12 | Y182T MUTATION T CELL ANTIGEN COUPLEUR AND METHODS AND USES THEREOF |
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| AU2018349093A1 true AU2018349093A1 (en) | 2020-05-28 |
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| AU (1) | AU2018349093A1 (ja) |
| CA (1) | CA3078637A1 (ja) |
| WO (1) | WO2019071358A1 (ja) |
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| CA3078637A1 (en) | 2017-10-12 | 2019-04-18 | Mcmaster University | T cell-antigen coupler with y182t mutation and methods and uses thereof |
| US10640562B2 (en) | 2018-07-17 | 2020-05-05 | Mcmaster University | T cell-antigen coupler with various construct optimizations |
| US11110123B2 (en) | 2018-07-17 | 2021-09-07 | Triumvira Immunologics Usa, Inc. | T cell-antigen coupler with various construct optimizations |
| US12016923B2 (en) | 2021-06-01 | 2024-06-25 | Triumvira Immunologics Usa, Inc. | Claudin 18.2 T cell-antigen couplers and uses thereof |
| US11453723B1 (en) * | 2021-06-25 | 2022-09-27 | Mcmaster University | BCMA T cell-antigen couplers and uses thereof |
| WO2023172931A2 (en) * | 2022-03-07 | 2023-09-14 | Triumvira Immunologics Usa, Inc. | Methods of treating her2 cancer with a her2 t cell-antigen coupler |
Family Cites Families (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2724320B1 (fr) | 1994-09-13 | 1996-12-20 | Transgene Sa | Nouvel implant pour le traitement des maladies acquises |
| ATE403001T1 (de) | 1996-05-22 | 2008-08-15 | Viventia Biotech Inc | Antigenbindungsfragmente die spezifisch krebszellen nachweisen, nukleotide die für diese fragmente kodieren, und deren verwendung zur vorbeugung und zum nachweis von krebs |
| GB9809658D0 (en) | 1998-05-06 | 1998-07-01 | Celltech Therapeutics Ltd | Biological products |
| US20030095967A1 (en) | 1999-01-25 | 2003-05-22 | Mackay Fabienne | BAFF, inhibitors thereof and their use in the modulation of B-cell response and treatment of autoimmune disorders |
| EP2314694A3 (en) | 1999-08-17 | 2013-12-11 | Biogen Idec MA Inc. | BAFF receptor (BCMA), an immunoregulatory agent |
| CA2408617A1 (en) | 2000-05-12 | 2001-11-22 | Amgen Inc. | Methods and compositions of matter concerning april/g70, bcma, blys/agp-3, and taci |
| JP2004533997A (ja) | 2001-02-20 | 2004-11-11 | ザイモジェネティクス，インコーポレイティド | Ｂｃｍａ及びｔａｃｉの両者を結合する抗体 |
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| WO2003072713A2 (en) | 2002-02-21 | 2003-09-04 | Biogen Idec Ma Inc. | Use of bcma as an immunoregulatory agent |
| US7820166B2 (en) | 2002-10-11 | 2010-10-26 | Micromet Ag | Potent T cell modulating molecules |
| CA2523716C (en) | 2003-05-31 | 2014-11-25 | Micromet Ag | Human anti-human cd3 binding molecules |
| BRPI0415457A (pt) | 2003-10-16 | 2006-12-05 | Micromet Ag | constructo de ligação especìfico de cd3 citotoxicamente ativo, seu processo de produção, composição compreendendo o mesmo, seqüência de ácido nucléico, vetor, hospedeiro, seus usos na preparação de uma composição farmacêutica e kit compreendendo os mesmo |
| BRPI0415709A (pt) | 2003-10-20 | 2006-12-19 | Biogen Idec Inc | esquemas terapêuticos para antagonistas de baff |
| JP2008525002A (ja) | 2004-12-23 | 2008-07-17 | ラボラトワール セローノ ソシエテ アノニム | Ｂｃｍａポリペプチド及びその使用 |
| CN105535967B (zh) | 2005-02-15 | 2022-05-03 | 杜克大学 | 抗cd19抗体及其在肿瘤学中的应用 |
| MX2008008046A (es) | 2005-12-21 | 2009-03-04 | Micromet Ag | Moleculas de epha2-bite y usos de las mismas. |
| SG10201504662WA (en) | 2006-06-14 | 2015-07-30 | Macrogenics Inc | Methods For The Treatment Of Autoimmune Disorders Using Immunosuppressive Monoclonal Antibodies With Reduced Toxicity |
| EP2119780B1 (en) | 2007-01-24 | 2015-03-25 | Kyowa Hakko Kirin Co., Ltd. | Genetically recombinant antibody composition having enhanced effector activity |
| WO2008119042A2 (en) | 2007-03-27 | 2008-10-02 | Zymogenetics, Inc. | Combination of blys inhibition and/or april inhibition and immunnosuppressants for treatment of autoimmune disease |
| WO2008131315A2 (en) | 2007-04-20 | 2008-10-30 | Amgen Inc. | Jacquelinidentification and method for using the pre-ligand assembly domain of the il-17 receptor |
| CA2738545A1 (en) | 2008-10-01 | 2010-04-08 | Micromet Ag | Cross-species-specific pscaxcd3, cd19xcd3, c-metxcd3, endosialinxcd3, epcamxcd3, igf-1rxcd3 or fapalpha xcd3 bispecific single chain antibody |
| EP3543256A1 (en) | 2009-01-12 | 2019-09-25 | Cytomx Therapeutics Inc. | Modified antibody compositions, methods of making and using thereof |
| MX341884B (es) | 2009-03-10 | 2016-09-07 | Biogen Ma Inc | Anticuerpos anti-antigeno de maduracion de celulas b (bcma). |
| US9273283B2 (en) * | 2009-10-29 | 2016-03-01 | The Trustees Of Dartmouth College | Method of producing T cell receptor-deficient T cells expressing a chimeric receptor |
| ES2621874T3 (es) | 2010-03-26 | 2017-07-05 | Memorial Sloan-Kettering Cancer Center | Anticuerpos para MUC16 y métodos de uso de los mismos |
| JP5985481B2 (ja) | 2010-09-01 | 2016-09-06 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | 抗イディオタイプ抗体の迅速な産生 |
| JP2014500879A (ja) | 2010-11-16 | 2014-01-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｂｃｍａ発現に相関性を有する疾患を治療する因子及び方法 |
| EP2670776B1 (en) | 2011-02-04 | 2018-11-21 | F. Hoffmann-La Roche AG | Fc VARIANTS AND METHODS FOR THEIR PRODUCTION |
| US20120213768A1 (en) | 2011-02-19 | 2012-08-23 | Baylor Research Institute | Diagnostic and Therapeutic Uses for B Cell Maturation Antigen |
| TWI622597B (zh) | 2011-03-28 | 2018-05-01 | 賽諾菲公司 | 具有交叉結合區定向之雙重可變區類抗體結合蛋白 |
| US20130101599A1 (en) | 2011-04-21 | 2013-04-25 | Boehringer Ingelheim International Gmbh | Bcma-based stratification and therapy for multiple myeloma patients |
| UA112434C2 (uk) | 2011-05-27 | 2016-09-12 | Ґлаксо Ґруп Лімітед | Антигензв'язувальний білок, який специфічно зв'язується з всма |
| ES2953190T3 (es) | 2011-05-27 | 2023-11-08 | Glaxo Group Ltd | Proteínas de unión a BCMA (CD269/TNFRSF17) |
| BR112014009925B1 (pt) | 2011-10-28 | 2022-09-20 | Teva Pharmaceuticals Australia Pty Ltd | Construtores de polipeptídeos e seus usos |
| TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對ｂｃｍａ之e3以及ｃｄ３的結合分子 |
| US9718893B2 (en) | 2011-12-19 | 2017-08-01 | Synimmune Gmbh | Bispecific antibody molecule |
| AU2013221672B2 (en) | 2012-02-13 | 2017-11-09 | Seattle Children's Hospital D/B/A Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
| WO2013132268A1 (en) | 2012-03-09 | 2013-09-12 | Ucl Business Plc | Chemical modification of antibodies |
| EP2872526B1 (en) | 2012-07-13 | 2020-04-01 | The Trustees of the University of Pennsylvania | Enhancing activity of car t cells by co-introducing a bispecific antibody |
| EP2953974B1 (en) | 2013-02-05 | 2017-12-20 | EngMab Sàrl | Bispecific antibodies against cd3epsilon and bcma |
| EP3019622A4 (en) | 2013-07-12 | 2017-06-14 | Zymeworks Inc. | Bispecific cd3 and cd19 antigen binding contructs |
| EP3060059A4 (en) | 2013-10-25 | 2017-11-01 | Board of Regents, The University of Texas System | Polyclonal gamma delta t cells for immunotherapy |
| KR102480433B1 (ko) | 2014-02-07 | 2022-12-21 | 맥마스터 유니버시티 | 3기능성 t 세포-항원 커플러 및 이의 제조 방법 및 용도 |
| EP3593812A3 (en) * | 2014-03-15 | 2020-05-27 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
| SI3280729T1 (sl) | 2015-04-08 | 2022-09-30 | Novartis Ag | Terapije CD20, terapije CD22 in kombinacija terapij s celico, ki izraža himerni antigenski receptor CD19 (CAR) |
| WO2016166139A1 (en) * | 2015-04-14 | 2016-10-20 | Eberhard Karls Universität Tübingen | Bispecific fusion proteins for enhancing immune responses of lymphocytes against tumor cells |
| US11059880B2 (en) * | 2015-06-30 | 2021-07-13 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Redirected cells with MHC chimeric receptors and methods of use in immunotherapy |
| EA038329B1 (ru) | 2015-08-28 | 2021-08-10 | Амьюникс Фармасьютикалз, Инк. | Химерный полипептидный комплекс и способы его получения и применения |
| US20210206826A1 (en) | 2015-11-19 | 2021-07-08 | The Regents Of The University Of California | Conditionally repressible immune cell receptors and methods of use thereof |
| WO2017106578A1 (en) | 2015-12-15 | 2017-06-22 | Amgen Inc. | Pacap antibodies and uses thereof |
| AU2017305524A1 (en) | 2016-08-04 | 2019-02-28 | Memorial Sloan-Kettering Cancer Center | Compositions and methods for immunotherapy |
| CN108250302A (zh) | 2016-12-29 | 2018-07-06 | 天津天锐生物科技有限公司 | 一种多功能蛋白质 |
| CA3078637A1 (en) | 2017-10-12 | 2019-04-18 | Mcmaster University | T cell-antigen coupler with y182t mutation and methods and uses thereof |
| SG11202100307WA (en) | 2018-07-17 | 2021-02-25 | Triumvira Immunologics Usa Inc | T cell-antigen coupler with various construct optimizations |
| US10640562B2 (en) | 2018-07-17 | 2020-05-05 | Mcmaster University | T cell-antigen coupler with various construct optimizations |
| US11110123B2 (en) | 2018-07-17 | 2021-09-07 | Triumvira Immunologics Usa, Inc. | T cell-antigen coupler with various construct optimizations |
| CN113490689B (zh) | 2019-02-01 | 2024-06-04 | 恺兴生命科技(上海)有限公司 | Tcr融合蛋白及表达tcr融合蛋白的细胞 |
| EP4240381A1 (en) | 2020-11-06 | 2023-09-13 | Mcmaster University | Cells comprising t cell-antigen couplers and uses thereof |
| US12016923B2 (en) | 2021-06-01 | 2024-06-25 | Triumvira Immunologics Usa, Inc. | Claudin 18.2 T cell-antigen couplers and uses thereof |
| US11453723B1 (en) | 2021-06-25 | 2022-09-27 | Mcmaster University | BCMA T cell-antigen couplers and uses thereof |
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| JP7227630B2 (ja) | 2023-02-22 |
| US11643472B2 (en) | 2023-05-09 |
| US20230265207A1 (en) | 2023-08-24 |
| CA3078637A1 (en) | 2019-04-18 |
| EP3694997A4 (en) | 2021-06-30 |
| CN111479925A (zh) | 2020-07-31 |
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